Our objective is to conduct studies on the epidemiology of age-related bone loss, osteoporosis, and fractures in women. The ability to make high precision measurements of bone density of the vertebrae and proximal femur by dual photon absorptiometry in subjects sampled from a well-characterized community population continues to serve as the foundation of this research project. Our first Specific Aim for the next five years is to expand our population-based studies on the natural history of and risk factors for age-related bone loss and fractures by accomplishing five investigational protocols. (i) We are making serial measurements of bone density over four years in a cohort of 81 postmenopausal women, who were between ages 51 to 70 years at entry, and relating the rate of bone loss to various behavioral, biochemical, and hormonal risk factors. These will be extended to eight years, during which time we calculate that one-third of the subjects will develop vertebral fractures. (ii) We will determine the prevalence and compute the incidence of vertebral fractures in women through a 10% random sample of the female population greater than or equal to 50 years of age. (iii) We will make a population-based, case-control study of vertebral fracture in women (240 cases and 340 controls). (iv) We will make a serial bone densitometric study across natural menopause in 50 perimenopausal women to search for causes of individual susceptibility to postmenopausal osteoporosis. (v) We will make serial densitometric measurements in 20 perimenopausal women after oophorectomy to test the hypothesis that quantitative differences exist between surgical and natural menopause which explain discrepant findings in the scientific literature. Our second Specific Aim is to compare the effectiveness of calcium supplementation and estrogen administration in preventing postmenopausal bone loss. For this, we will make a 2 x 2 factorial, three-year clinical trial in 100 postmenopausal women. There will be 25 women in each of four groups receiving estrogen and placebo, calcium and placebo, estrogen and calcium, and placebo alone. The dosage of calcium will be 1,500 mg/day. Estrogen will be given by a novel transdermal method which will reproduce premenopausal follicular phase levels of this steroid yet will reduce or eliminate the risks from estrogen administration. This research proposal should provide crucial information for defining individuals at risk for osteoporosis and for developing safe, effective and low-cost strategies for fracture prevention.